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Cited by 226

Novel 3D Culture Systems for Studies of Human Liver Function and Assessments of the Hepatotoxicity of Drugs and Drug Candidates

Lauschke, Volker M., Hendriks, Delilah F. G., Bell, Catherine C., Andersson, Tommy B., Ingelman-Sundberg, Magnus·2016·Chemical Research in Toxicology
DOI 10.1021/acs.chemrestox.6b00150
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Abstract

The liver is an organ with critical importance for drug treatment as the disposition and response to a given drug is often determined by its hepatic metabolism. Patient-specific factors can entail increased susceptibility to drug-induced liver injury, which constitutes a major risk for drug development programs causing attrition of promising drug candidates or costly withdrawals in postmarketing stages. Hitherto, mainly animal studies and 2D hepatocyte systems have been used for the examination of human drug metabolism and toxicity. Yet, these models are far from satisfactory due to extensive species differences and because hepatocytes in 2D cultures rapidly dedifferentiate resulting in the loss of their hepatic phenotype and functionality. With the increasing comprehension that 3D cell culture systems more accurately reflect in vivo physiology, in the recent decade more and more research has focused on the development and optimization of various 3D culture strategies in an attempt to preserve liver properties in vitro. In this contribution, we critically review these developments, which have resulted in an arsenal of different static and perfused 3D models. These systems include sandwich-cultured hepatocytes, spheroid culture platforms, and various microfluidic liver or multiorgan biochips. Importantly, in many of these models hepatocytes maintain their phenotype for prolonged times, which allows probing the potential of newly developed chemical entities to cause chronic hep…

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Authors
Lauschke, V. M., Hendriks, D. F. G., Bell, C. C., Andersson, T. B., & Ingelman-Sundberg, M.
Affiliations
Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, SE-17177 Stockholm, Sweden
Venue
Chemical Research in Toxicology
Publisher
American Chemical Society (ACS)
Published
2016-09-23
Volume
29
Issue
12
Pages
1936-1955
ISSN
  • 0893-228X
  • 1520-5010
DOI
10.1021/acs.chemrestox.6b00150
Cited by
226
References
19
Language
en
Funders
  • AstraZeneca
  • Vetenskapsr?det
  • European Commission (115336)
  • Directorate-General for Research and Innovation

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